Tryptone-stabilized gold nanoparticles target tubulin and inhibit cell viability by inducing an unusual form of cell cycle arrest
| Autor: | Tejashree Mahaddalkar, Sanith Cheriyamundath, H. Muthurajan, Sourabh Mehta, Manu Lopus |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Cell Survival Metal Nanoparticles Apoptosis HeLa Mice 03 medical and health sciences Drug Stability Tubulin Microtubule Cell Line Tumor medicine Animals Humans Molecular Targeted Therapy Viability assay biology Cell Cycle Cell Cycle Checkpoints Cell Biology Cell cycle biology.organism_classification Tubulin Modulators Cell biology 030104 developmental biology Mechanism of action Peptones NIH 3T3 Cells biology.protein Gold medicine.symptom HeLa Cells |
| Zdroj: | Experimental Cell Research. 360:163-170 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2017.09.002 |
| Popis: | Gold nanoparticles have been investigated extensively for their molecular mechanisms of action and anticancer potential. We report a novel, tubulin-targeted antiproliferative mechanism of action of tryptone-stabilized gold nanoparticles (TsAuNPs). TsAuNPs, synthesized using HAuCl4·3H2O and tryptone and characterized by a variety of spectroscopic methods and transmission electron microscopy, were found to be inhibitory to viability of human pancreatic (PANC-1), cervical (HeLa), and breast (MDA-MB-231) cancer cell lines in a concentration-dependent manner, with highest efficacy against PANC-1 cells. The particles strongly inhibited the clonogenic propagation of PANC-1 cells. TsAuNPs-mediated inhibition of cell viability involved an unusual mode of cell cycle arrest (arrest at both G0/G1 phase and S-phase) followed by apoptosis. In vitro, TsAuNPs bound purified tubulin, competitively inhibited anilinonaphthalene sulfonate binding to tubulin, and suppressed tubulin assembly. In cells, tubulin-TsAuNPs interactions were manifested as a disrupted microtubule network, defective reassembly of cold-disassembled microtubules, and induction of tubulin acetylation. Our data indicate that TsAuNPs inhibit cell viability by inducing differential cell cycle arrest possibly through disrupted dynamicity of cellular microtubules. |
| Databáze: | OpenAIRE |
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